IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection

Irini Sereti, Richard M. Dunham, John Spritzler, Evgenia Aga, Michael A. Proschan, Kathy Medvik, Catherine A. Battaglia, Alan L. Landay, Savita Pahwa, Margaret A. Fischl, David M. Asmuth, Allan R. Tenorio, John D. Altman, Lawrence Fox, Susan Moir, Angela Malaspina, Michel Morre, Renaud Buffet, Guido Silvestri, Michael M. Lederman

Research output: Contribution to journalArticle

233 Scopus citations

Abstract

Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human IL-7 (rhIL-7) administration were therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 μg/kg and a maximum tolerated dose of 30 μg/kg. Injection site reactions and transient elevations of liver function tests were the most notable side effects. Transient increases in plasma HIV-RNA levels were observed in 6 of 11 IL-7-treated patients. Recombinant hIL-7 induced CD4 and CD8 T cells to enter cell cycle; cell-cycle entry was also confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to transient down-regulation of the IL-7 receptor alpha chain (CD127) in both CD4+ and CD8+ T cells. Single-dose rhIL-7 increased the numbers of circulating CD4+ and CD8+ T cells, predominantly of central memory phenotype. The frequency of CD4 + T cells with a regulatory T-cell phenotype (CD25high CD127low) did not change after rhIL-7 administration. Thus, rhIL-7 has a biologic and toxicity profile suggesting a potential for therapeutic trials in HIV infection and other settings of lymphopenia. This clinical trial has been registered at http:// www.clinicaltrials.gov under NCT0099671.

Original languageEnglish (US)
Pages (from-to)6304-6314
Number of pages11
JournalBlood
Volume113
Issue number25
DOIs
StatePublished - Nov 19 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Sereti, I., Dunham, R. M., Spritzler, J., Aga, E., Proschan, M. A., Medvik, K., Battaglia, C. A., Landay, A. L., Pahwa, S., Fischl, M. A., Asmuth, D. M., Tenorio, A. R., Altman, J. D., Fox, L., Moir, S., Malaspina, A., Morre, M., Buffet, R., Silvestri, G., & Lederman, M. M. (2009). IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood, 113(25), 6304-6314. https://doi.org/10.1182/blood-2008-10-186601